|WEEK #||TOPICS||LECTURE SUMMARIES|
Instructors and students will introduce themselves. The instructors will then present the course syllabus and how to search for scientific publications using PubMed.
The instructors will then give an introductory lecture presenting the key cells and processes involved in vascular development.
|2||Visualization of angiogenic sprouting||What controls the pattern of developing blood vessels? How do new branches arise? What controls the size of a new branch and the direction of its growth? We will discuss how imaging of the blood vessels in the retina identified the growth factor VEGF as a critical regulator of vascular patterning.|
|3||Lessons from transgenic mice|| |
Novel gene technologies have allowed the manipulation of gene expression in mice in a time-controllable manner. Homologous or site-specific recombination in embryonic stem cells allows study of the consequences of deficiencies, mutations, and conditional or tissue-specific expression of gene products in transgenic mice.
During this session we will discuss the advantages and limitations of the use of mouse models to study the function genes in vivo.
|4||Intravital imaging of zebrafish||The zebrafish has recently emerged as an important model for the study of vascular development. Its genetic accessibility and optically clear embryo have allowed researchers for the first time to perform single cell live imaging of blood vessels in vivo. During this session, we will discuss how blood vessel lumens are formed and how zebrafish have been utilized to address key questions in vascular biology.|
|5||The importance of pericytes and smooth muscle cells||New blood vessels are initially formed through the assembly or sprouting of endothelial cells, but the recruitment of pericytes (mesenchymal-like cells associated with the wall of blood vessels) and vascular smooth muscle cells (called mural cells) ensures the formation of a mature and stable vascular network. In this session, we will discuss how defective mural-cell coverage is associated with the poorly organized and leaky vasculature seen in tumors and other human diseases and examine some of the key molecular regulators of mural cell recruitment and signaling.|
|6||Angiogenesis in disease and medicine|| |
Pathological angiogenesis in the retina is a major cause of blindness. Over 1.5 million US residents have been diagnosed with age-related macular degeneration (AMD), a disease caused by the growth of leaky bloody vessel beneath the retina. In this session, we will discuss the therapeutic strategies being used to treat AMD and the causes of neovascularization in individuals with diabetes.
During this session, the instructors will introduce the students to the use of Powerpoint software and give them tips for an effective oral presentation.
|7||Tumor angiogenesis – A historical perspective||In 1971, Judah Folkman proposed that the growth of tumors could be suppressed by cutting off the blood supply. At the time, he faced skepticism and even ridicule from the scientific community. Today, more than 1000 laboratories worldwide are engaged in the study of angiogenesis and anti-angiogenic therapies to prevent the spread of cancer. In this session, we will discuss the advances that have been made in the imaging of tumor angiogenesis and the identification of anti-angiogenic factors as well as the importance of developing novel technologies.|
|8||Cutting cancer's supply lines: Targeting the VEGF pathway|| |
In the two following sessions, we will discuss successful strategies aimed at targeting tumor vasculature alone or in combination with classical anti-cancer therapy (radiotherapy/chemotherapy). In this session, we will discuss different approaches aimed at targeting the VEGF signaling pathway.
Bevacizumab (or Avastin), a humanized monoclonal antibody targeting VEGF has successfully been used alone or in combination with classical anti-cancer therapies and has been the first clinically available angiogenesis inhibitor in the United States. Other compounds are aimed at targeting downstream steps of the VEGF pathway such as blocking the VEGFR activity.
|9||Cutting cancer's supply lines: The example of the angiostatin||Angiostatin is a 38 kDa fragment of plasmin, a protein naturally found in the plasma and which function is to degrade plasma proteins. Angiostatin has been shown to be an endogenous angiogenesis inhibitor, and several therapeutic strategies have been developed using this compound. In this session, we will discuss two successful trials that combined angiostatin-based therapy with conventional anti-cancer therapies.|
|10||How can anti-angiogenic therapies stimulate rather than inhibit tumor growth and spreading?||Despite the continual optimism that targeting tumor angiogenesis will prevent the growth and spread of cancer, a number of recent studies have found that anti-angiogenic therapies are inefficacious and in some cases can facilitate the spread of cancer. This session will examine the controversy surrounding the development of drugs that target tumor angiogenesis.|
|11||Field trip|| |
Microscopic analysis of the vasculature at the Koch Institute for Integrative Cancer Research.
The development of high resolution imaging techniques to visualize developing blood vessels has transformed the angiogenesis field. On this field trip you will use fluorescence microscopy to examine the vasculature of developing embryos and analyze and interpret data from confocal microscopy images using 3D rendering computational software.
|12||Serendipity!||Science is sometimes about serendipity and luck. In this last session, we will discuss two fortunate and unexpected discoveries in the field of tumor angiogenesis that have led to development of potential cancer therapies.|
|13||Oral presentations||Students will give a 15 minute PowerPoint presentation of a paper from a selection provided by the instructors. The presentations will be given to the entire group. Students will be encouraged to actively participate in a discussion following each presentation.|